Serum anti-DIDO1, anti-CPSF2, and anti-FOXJ2 antibodies as predictive risk markers for acute ischemic stroke

Takaki Hiwasa, Hao Wang, Ken ichiro Goto, Seiichiro Mine, Toshio Machida, Eiichi Kobayashi, Yoichi Yoshida, Akihiko Adachi, Tomoo Matsutani, Mizuki Sata, Kazumasa Yamagishi, Hiroyasu Iso, Norie Sawada, Shoichiro Tsugane, Mitoshi Kunimatsu, Ikuo Kamitsukasa, Masahiro Mori, Kazuo Sugimoto, Akiyuki Uzawa, Mayumi MutoSatoshi Kuwabara, Yoshio Kobayashi, Mikiko Ohno, Eiichiro Nishi, Akiko Hattori, Masashi Yamamoto, Yoshiro Maezawa, Kazuki Kobayashi, Ryoichi Ishibashi, Minoru Takemoto, Koutaro Yokote, Hirotaka Takizawa, Takashi Kishimoto, Kazuyuki Matsushita, Sohei Kobayashi, Fumio Nomura, Takahiro Arasawa, Akiko Kagaya, Tetsuro Maruyama, Hisahiro Matsubara, Minako Tomiita, Shinsaku Hamanaka, Yushi Imai, Tomoo Nakagawa, Naoya Kato, Jiro Terada, Takuma Matsumura, Yusuke Katsumata, Akira Naito, Nobuhiro Tanabe, Seiichiro Sakao, Koichiro Tatsumi, Masaaki Ito, Fumiaki Shiratori, Makoto Sumazaki, Satoshi Yajima, Hideaki Shimada, Mikako Shirouzu, Shigeyuki Yokoyama, Takashi Kudo, Hirofumi Doi, Katsuro Iwase, Hiromi Ashino, Shu Yang Li, Masaaki Kubota, Go Tomiyoshi, Natsuko Shinmen, Rika Nakamura, Hideyuki Kuroda, Yasuo Iwadate

研究成果: Article査読

抄録

Background: Acute ischemic stroke (AIS) is a serious cause of mortality and disability. AIS is a serious cause of mortality and disability. Early diagnosis of atherosclerosis, which is the major cause of AIS, allows therapeutic intervention before the onset, leading to prevention of AIS. Methods: Serological identification by cDNA expression cDNA libraries and the protein array method were used for the screening of antigens recognized by serum IgG antibodies in patients with atherosclerosis. Recombinant proteins or synthetic peptides derived from candidate antigens were used as antigens to compare serum IgG levels between healthy donors (HDs) and patients with atherosclerosis-related disease using the amplified luminescent proximity homogeneous assay-linked immunosorbent assay. Results: The first screening using the protein array method identified death-inducer obliterator 1 (DIDO1), forkhead box J2 (FOXJ2), and cleavage and polyadenylation specificity factor (CPSF2) as the target antigens of serum IgG antibodies in patients with AIS. Then, we prepared various antigens including glutathione S-transferase-fused DIDO1 protein as well as peptides of the amino acids 297–311 of DIDO1, 426–440 of FOXJ2, and 607–621 of CPSF2 to examine serum antibody levels. Compared with HDs, a significant increase in antibody levels of the DIDO1 protein and peptide in patients with AIS, transient ischemic attack (TIA), and chronic kidney disease (CKD) but not in those with acute myocardial infarction and diabetes mellitus (DM). Serum anti-FOXJ2 antibody levels were elevated in most patients with atherosclerosis-related diseases, whereas serum anti-CPSF2 antibody levels were associated with AIS, TIA, and DM. Receiver operating characteristic curves showed that serum DIDO1 antibody levels were highly associated with CKD, and correlation analysis revealed that serum anti-FOXJ2 antibody levels were associated with hypertension. A prospective case–control study on ischemic stroke verified that the serum antibody levels of the DIDO1 protein and DIDO1, FOXJ2, and CPSF2 peptides showed significantly higher odds ratios with a risk of AIS in patients with the highest quartile than in those with the lowest quartile, indicating that these antibody markers are useful as risk factors for AIS. Conclusions: Serum antibody levels of DIDO1, FOXJ2, and CPSF2 are useful in predicting the onset of atherosclerosis-related AIS caused by kidney failure, hypertension, and DM, respectively.

本文言語English
論文番号131
ジャーナルBMC Medicine
19
1
DOI
出版ステータスPublished - 2021 12

ASJC Scopus subject areas

  • 医学(全般)

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